Clinical and laboratory studies are conducted to determine etiology (infection, immunity and/or genetics) for chronic diseases of the peripheral and central nervous system. Current studies include amyotrophic lateral sclerosis, (ALS), polymyositis/dermatomyositis, demyelinating polyneuropathies and chronic Guillain-Barre syndrome, Reye's syndrome, multiple sclerosis, progressive multifocal leukoencephalopathy, subacute sclerosing panencephalitis and myasthenia gravis. Combined clinical data, genetic information, HLA and MLC typing virus serology and virus isolation studies are obtained for these studies. The nature of oligoclonal bands found in the CSF of patients with chronic neurological diseases in under investigation. A neuromuscular disease that occurs in patients who have had poliomyelitis at an early age has clinically defined; the possiblity that this might be due to a late polio virus infection or an abnormal immunoregulation and an immune reaction to neuronal cells is under investigation. Abnormalities in lymphocyte subpopulations have been detected in patients with paraproteinemic polyneuropathies; IgM monoclonal band has been identified in the spinal fluid of some of these patients and an abnormal blood-CSF and nerve barrier was found. The metabolic activity of the cortex in ALS patients is being studied using the PET scan and 18F 2-deoxy-D-glucose; hypometabolism was demonstrated not only in the motor but also in the paramotor and sensory cortex, suggesting that ALS is a rather generalized process affecting many cortical regions. Using recombinant DNA alpha2-interferon, an experimental therapeutic trial is being started in ALS patients. Virological studies were performed in patients with Reye's syndrome and their families and their ability to handle a salicylate challenge was investigated.